Severe nerve injuries may result in significant gaps and surgical management of nerve defects is still a major challenge. When direct repair of the injured nerve with epineural sutures is impossible, the defect between the nerve stumps has to be bridged by a conduit of some kind, which will facilitate axonal regeneration towards the distal nerve stump. Currently, the microsurgical techniques used for the repair of peripheral nerve defects do not always result in optimal functional outcome. The most reliable and widely used method is bridging the defect by an autograft, which is considered the gold standard for nerve gap repair (Watchmaker, G P et al., Clin. Plast. Surg, 24:63-73 (1997); Siemionow, M., et al., Ann. Plast. Surg., 52:72-79 (2004)). Autografts can be obtained from functionally less important cutaneous sensory nerves such as a sural nerve, medial antebrachial cutaneous nerve, saphenous nerve, superficial radial nerve and lateral antebrachial cutaneous nerve, which are associated with some donor site morbidity such as scarring, anesthesia, neuroma formation (Brandt, J., et al., J. Hand Surg. [Br], 24:284-290 (1999); MacKinnon, S E, Ann. Plast. Surg., 22:257-273 (1989)). There is also a limited source of donor nerves available that makes reconstruction of large nerve defects difficult. Nerve allografts have been studied experimentally and used clinically, however the major disadvantage is the need for immunosuppression to prevent rejection (Mackinnon, S E., Plast. Reconstr. Surg. 107:1419-1429 (2001); Fox, I K, Muscle Nerve, 31:59-69 (2005)). Therefore nerve allografts are used only in selected cases and are not the primary choice of peripheral nerve repair in clinical practice.
Various natural and synthetic conduit materials have been investigated as an alternative technique to nerve autografts. Vein grafts, collagen, muscle, denaturated muscle basal lamina, tendon, mesothelium, amnion and epineural sheaths are the natural conduits investigated by researchers (Tang, J B, J. Reconstr. Microsurg., 11:21-26 (1995); Mohammad, J., Plast. Reconstr. Surg., 105:660-666 (2000); Chen, L E, J. Reconstr. Surg., 10:137-144 (1994); Atabay, K., et al., Plast. Surg. Forum, 18:121 (1995); Siemionow, M., et al., Ann. Plast. Surg., 48:281-285 (2002); Tetik, C., et al., Ann. Plast. Surg., 49:397-403 (2002); Ayhan, S., et al., J. Reconstr. Microsurg., 16:371-378 (2000); Yavuzer, R., et al., Ann Plast. Surg., 48:392-400 (2002); Lundborg, G., et al., J Hand Surg. [Am], 7:580-587 (1982); Archibald, S J., et al., J. Comp. Neurol., 306:685-696 (1991); Keskin, M., et al., Plast, Reconstr. Surg., 113:1372-1379 (2004)). Synthetic materials for bridging the defect have gained attention and silicon tubes, polylactic acid, polyglycolic acid, poly-3-hydroxybutyrate, polyurethane, and poly(organo)phosphazene tubes were used in experimental and clinical studies with encouraging results (Hudson, T W, et al., Clin. plast. Surg., 26:485-497 (1999); Langone, F., et al., Biomaterails, 16:347-353 (1995); Lundborg, G., et al., Exp. Neurol., 76:361-375 (1982); Weber, R A., et al., Plast. Reconstr. Surg, 106:1036-1045 (2000); Hazari, A., et. al., Br. J. Plast. Surg., 52:653-657 (1999); Navissano, M., et al., Micorsurgery, 25:268-271 (2005); Nalamura, T., et al., Brain Res., 1027:18-29 (2004)). These conduits are used as tubulized chambers and present with different advantages, but also disadvantages such as inflammation, foreign body reaction, compression, and toxicity of degradation products.
Alternative methods and compositions with less morbidity for treating nerve injuries are needed.